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European Journal of Drug Metabolism and Pharmacokinetics

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https://www.readbyqxmd.com/read/29134502/the-influence-of-compatibility-of-rhubarb-and-radix-scutellariae-on-the-pharmacokinetics-of-anthraquinones-and-flavonoids-in-rat-plasma
#1
Yaqing Zhang, Zunjian Zhang, Rui Song
BACKGROUND AND OBJECTIVES: Rhubarb-Radix scutellariae is a classic herb pair, which is commonly used to clear away heat and toxin in clinic. The aim of this study was to investigate the influence of compatibility of Rhubarb and Radix scutellariae on the pharmacokinetic behaviors of anthraquinones and flavonoids in rat plasma. METHODS: Eighteen rats were randomly divided into three groups, and were orally administered Rhubarb and/or Radix scutellariae extracts. A sensitive and rapid UPLC-MS/MS method was developed and validated to determine the concentrations of baicalin, baicalein, wogonside, wogonin, rhein, and emodin in rat plasma...
November 14, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29134501/pharmacokinetic-properties-of-saffron-and-its-active-components
#2
Azar Hosseini, Bibi Marjan Razavi, Hossein Hosseinzadeh
Saffron as a medicinal plant has many therapeutic effects. Phytochemical studies have reported that saffron is composed of at least four active ingredients which include crocin, crocetin, picrocrocin and safranal. The carotenoids of saffron are sensitive to oxygen, light, heat and enzymatic oxidization. However, regulation of these factors is required for saffron quality. Some pharmacologic effects of saffron and its active compounds include cardioprotective, neuroprotective, memory enhancer, antidepressant and anxiolytic...
November 13, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29119333/physiologically-based-pharmacokinetic-modelling-of-cytochrome-p450%C3%A2-2c9-related-tolbutamide-drug-interactions-with-sulfaphenazole-and-tasisulam
#3
Everett J Perkins, Maria Posada, P Kellie Turner, Jill Chappell, Wee Teck Ng, Chris Twelves
BACKGROUND AND OBJECTIVES: Cytochrome P450 2C9 (CYP2C9) is involved in the biotransformation of many commonly used drugs, and significant drug interactions have been reported for CYP2C9 substrates. Previously published physiologically based pharmacokinetic (PBPK) models of tolbutamide are based on an assumption that its metabolic clearance is exclusively through CYP2C9; however, many studies indicate that CYP2C9 metabolism is only responsible for 80-90% of the total clearance. Therefore, these models are not useful for predicting the magnitude of CYP2C9 drug-drug interactions (DDIs)...
November 8, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29116616/correction-to-continuous-infusion-versus-intermittent-bolus-of-beta-lactams-in-critically-ill-patients-with-respiratory-infections-a-systematic-review-and-meta-analysis
#4
Young R Lee, Pamela D Miller, Saeed K Alzghari, Delilah D Blanco, Jackson D Hager, Kailey S Kuntz
Unfortunately, ≥ was found missing between scores and 20 in conclusion section of the online published article. The original article was corrected.
November 7, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29101732/a-review-of-the-clinical-pharmacokinetics-and-pharmacodynamics-of-isavuconazole
#5
Kyle John Wilby
Invasive fungal infections are a major cause of morbidity and mortality, especially for immunocompromised patients. Treatment options are few and most are limited by safety and formulation concerns. Isavuconazole is a new triazole antifungal agent with official indications for the treatment of invasive fungal infections caused by Aspergillus and Mucormycosis. Its clinical efficacy has been proven in two landmark trials, SECURE and VITAL. This review aims to summarize and evaluate the published literature reporting clinical pharmacokinetic and pharmacodynamic outcome data of isavuconazole in humans...
November 4, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29076028/safety-tolerability-and-pharmacokinetics-of-oral-bi-425809-a-glycine-transporter-1-inhibitor-in-healthy-male-volunteers-a-partially-randomised-single-blind-placebo-controlled-first-in-human-study
#6
Viktoria Moschetti, Michael Desch, Sophia Goetz, Karl-Heinz Liesenfeld, Holger Rosenbrock, Klaus-Peter Kammerer, Glen Wunderlich, Sven Wind
BACKGROUND AND OBJECTIVES: Schizophrenia and Alzheimer's disease are characterised by glutamatergic pathway abnormalities related to N-methyl-D-aspartate (NMDA) receptor hypofunction and cognitive impairment. Glycine is an NMDA receptor co-agonist; inhibition of glycine transporter 1 (GlyT1) should improve NMDA receptor hypofunction. This study evaluated safety and pharmacokinetic properties of BI 425809-a potent and selective GlyT1 inhibitor. METHODS: In the single-rising dose (SRD) component of this study, subjects were randomised to a single dose of BI 425809 [doses (mg): 0...
October 26, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29039071/potential-applications-of-gliclazide-in-treating-type-1-diabetes-mellitus-formulation-with-bile-acids-and-probiotics
#7
Momir Mikov, Maja Đanić, Nebojša Pavlović, Bojan Stanimirov, Svetlana Goločorbin-Kon, Karmen Stankov, Hani Al-Salami
A major advancement in therapy of type 1 diabetes mellitus (T1DM) is the discovery of new treatment which avoids and even replaces the absolute requirement for injected insulin. The need for multiple drug therapy of comorbidities associated with T1DM increases demand for developing novel therapeutic alternatives with new mechanisms of actions. Compared to other sulphonylurea drugs used in the treatment of type 2 diabetes mellitus, gliclazide exhibits a pleiotropic action outside pancreatic β cells, the so-called extrapancreatic effects, such as antiinflammatory and cellular protective effects, which might be beneficial in the treatment of T1DM...
October 16, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29027128/continuous-infusion-versus-intermittent-bolus-of-beta-lactams-in-critically-ill-patients-with-respiratory-infections-a-systematic-review-and-meta-analysis
#8
REVIEW
Young R Lee, Pamela D Miller, Saeed K Alzghari, Delilah D Blanco, Jackson D Hager, Kailey S Kuntz
BACKGROUND: Critically ill patients display altered pharmacokinetics and pharmacodynamics and are more likely to be infected with more resistant pathogens. Beta-lactam antibiotics exhibit time-dependent pharmacodynamics; therefore, it is postulated that continuous infusion (CI) may optimize these parameters. OBJECTIVE: To perform a systematic review and meta-analysis of the available literature comparing CI versus intermittent bolus (IB) of beta-lactam antibiotics in critically ill adult patients with respiratory infections to determine if clinical benefits exist...
October 12, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29019074/in-vitro-inhibitory-effect-of-gymnema-sylvestre-extracts-and-total-gymnemic-acids-fraction-on-select-cytochrome-p450-activities-in-rat-liver-microsomes
#9
Madhuri Vaghela, Krishna Iyer, Nancy Pandita
BACKGROUND AND OBJECTIVES: Gymnema sylvestre R. Br. is a well-known Indian medicinal herb. Gymnemic acids are pentacyclic triterpenes saponins and active phytoconstituents of Gymnema sylvestre. The study aimed at evaluation of the in vitro rat liver cytochrome P450 (CYP) inhibition potential of extracts and total gymnemic acid (TA)-enriched fractions from G. sylvestre. METHODS: Standardization of G. sylvestre [ethanolic (EL), hydroethanolic (HE), total acid of ethanolic (TAE), total acid of hydroethanolic (TAHE) and total acid of aqueous (TAAQ) extract] was done with respect to deacyl gymnemic acid (DAGA), using reverse phase-high performance liquid chromatography (RP-HPLC)...
October 10, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29019020/pharmacodynamic-and-pharmacokinetic-markers-for-anti-angiogenic-cancer-therapy-implications-for-dosing-and-selection-of-patients
#10
Matteo Morotti, Prashanth Hari Dass, Adrian L Harris, Simon Lord
Angiogenesis is integral to tumour growth and invasion, and is a key target for cancer therapeutics. However, for many of the licensed indications, only a modest clinical benefit has been observed for both monoclonal antibody and small-molecule tyrosine kinase inhibitor anti-angiogenic therapy. Pre-clinical and clinical studies have attempted to evaluate circulating, imaging, genomic, pharmacokinetic, and pharmacodynamic markers that may aid both the selection of patients for treatment and define dosing. Correct dosing is likely to be critical in the context of vascular normalization to allow better delivery of concomitant anti-cancer therapy and novel imaging techniques hold much promise in the early evaluation of pharmacodynamic response to improve efficacy...
October 10, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28956285/antiretroviral-therapy-and-alcohol-interactions-x-raying-testicular-and-seminal-parameters-under-the-haart-era
#11
Oluwatosin O Ogedengbe, Edwin C S Naidu, Onyemaechi O Azu
The prevalence of alcohol use among HIV-infected patients undergoing antiretroviral (ARV) treatments has raised several concerns related to key therapeutic indices. These include drug interactions, compliance, efficacy and toxicity with the possibility of accelerated disease progression. Interaction of ARVs with alcohol can result in therapeutic failures or place patients at significant risk for toxicities. Research findings in this particular area are, however, limited and sometimes conflicting. This review focuses on alcohol and ARV interactions affecting testicular and spermatogenic indices...
September 27, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28929443/short-term-fasting-alters-pharmacokinetics-of-cytochrome-p450-probe-drugs-does-protein-binding-play-a-role
#12
Laureen A Lammers, Roos Achterbergh, Johannes A Romijn, Ron A A Mathôt
BACKGROUND AND OBJECTIVES: Short-term fasting differentially alters cytochrome P450 (CYP) mediated drug metabolism. This has been established by using CYP-enzyme selective probe drugs. However, the observed effects of fasting on the pharmacokinetics of these probe drugs may also include the effects of altered plasma protein binding of these drugs. Therefore, we studied the effect of short-term fasting on protein binding of five commonly used probe drugs [caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and S-warfarin (CYP2C9)]...
September 19, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28916980/pharmacokinetics-of-panax-notoginseng-saponins-in-adhesive-and-normal-preparation-of-fufang-danshen
#13
Xiao-Nan Chen, Dan-Qi Li, Meng-di Zhao, Gang-Yan Yu, Shou-Ying Du, Yang Lu, Jie Bai, Peng-Yue Li, Ya-Li Wu, Zhi-Hao Tian, Yan-Ying Zeng
BACKGROUND AND OBJECTIVE: Fufang Danshen formula, a famous Chinese patent medicine containing Salvia miltiorrhiza, Panax notoginseng and borneol, has been widely used in the treatment of coronary heart disease. The application is restricted by low bioavailability partly due to Panax notoginseng saponins (PNS) instability and low in vivo absorption. Thus, adhesive pellets were developed to improve bioavailability. The objectives of the present study were to evaluate the adhesive preparation by describing PNS's plasma pharmacokinetics in vivo and compare adhesive micro pills with normal preparation...
September 15, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28916907/pharmacokinetic-study-of-piracetam-in-focal-cerebral-ischemic-rats
#14
Pankaj Paliwal, Debabrata Dash, Sairam Krishnamurthy
BACKGROUND AND OBJECTIVE: Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion...
September 15, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28913815/pharmacokinetic-pharmacodynamic-analysis-of-cisplatin-with-hydration-and-mannitol-diuresis-the-contribution-of-urine-cisplatin-concentration-to-nephrotoxicity
#15
Keizo Fukushima, Akira Okada, Hiroyuki Oe, Mika Hirasaki, Mami Hamori, Asako Nishimura, Nobuhito Shibata, Nobuyuki Sugioka
BACKGROUND AND OBJECTIVES: Forced diuresis, high-volume hydration with diuresis, is widely used as a prophylactic treatment against cisplatin nephrotoxicity. However, the details of the underlying mechanisms and the optimal protocol of forced diuresis remain unclear. The present study investigated the alterations in pharmacokinetics and pharmacodynamics (nephrotoxicity) of cisplatin with forced diuresis treatment. METHODS: Cisplatin (5 mg/kg) was intravenously injected to rats (5 rats/group, except for control group in pharmacodynamic study, n = 13) treated with or without forced diuresis 2-h pre- and post-hydration with 10% mannitol at different infusion rates (0...
September 14, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28895074/in-vitro-comparison-of-the-role-of-p-glycoprotein-and-breast-cancer-resistance-protein-on-direct-oral-anticoagulants-disposition
#16
Sophie Hodin, Thierry Basset, Elodie Jacqueroux, Olivier Delezay, Anthony Clotagatide, Nathalie Perek, Patrick Mismetti, Xavier Delavenne
BACKGROUND: Pharmacokinetics of direct oral anticoagulants (DOACs) are influenced by ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). OBJECTIVES: To better understand the role of transporters in DOAC disposition, we evaluated and compared the permeabilities and transport properties of these drugs. METHODS: Bidirectional permeabilities of DOACs were investigated across Caco-2 cells monolayer...
September 11, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28890991/comments-on-population-pharmacokinetic-modeling-of-olmesartan-the-active-metabolite-of-olmesartan-medoxomil-in-patients-with-hypertension
#17
LETTER
Nuggehally R Srinivas
No abstract text is available yet for this article.
December 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28547295/high-loading-dose-of-microencapsulated-gliclazide-formulation-exerted-a-hypoglycaemic-effect-on-type-1-diabetic-rats-and-incorporation-of-a-primary-deconjugated-bile-acid-diminished-the-hypoglycaemic-antidiabetic-effect
#18
Svetlana Golocorbin-Kon, Jelena Calasan, Boris Milijasevic, Sasa Vukmirovic, Mladena Lalic-Popovic, Momir Mikov, Hani Al-Salami
BACKGROUND AND OBJECTIVE: Gliclazide is a drug commonly used in type 2 diabetes mellitus. Recently, gliclazide has shown desirable pharmacological effects such as immunoregulatory and anti-clotting effects, which suggests potential applications in type 1 diabetes mellitus (T1DM). Gliclazide has variable absorption after oral administration, and thus using targeted-delivery techniques, such as microencapsulation, may optimise gliclazide absorption and potential applications in T1DM. Bile acids such as cholic acid have shown microcapsule-stabilising and controlled-release effects, and thus their incorporation into gliclazide microcapsules may further optimise gliclazide release, absorption and antidiabetic effects...
December 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28536776/development-of-improved-dosing-regimens-for-mycophenolate-mofetil-based-on-population-pharmacokinetic-analyses-in-adults-with-lupus-nephritis
#19
Azrin N Abd Rahman, Susan E Tett, Halim A Abdul Gafor, Brett C McWhinney, Christine E Staatz
BACKGROUND AND OBJECTIVE: Mycophenolic acid (MPA) provides effective treatment for lupus nephritis patients. Owing to its large pharmacokinetic variability, it is questionable whether standard fixed dose therapy can achieve optimal MPA exposure. The aim of this study was to develop a population pharmacokinetic model of MPA and its metabolite, 7-O-MPA-β-glucuronide (MPAG), to identify important covariate influences and better predict patient dosing requirements. METHODS: MPA and MPAG concentration-time profiles were collected from 25 patients receiving mycophenolate mofetil (MMF) with or without cyclosporine (CsA) co-therapy...
December 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28536775/catechol-o-methyltransferase-and-udp-glucuronosyltransferases-in-the-metabolism-of-baicalein-in-different-species
#20
Ruiya Zhang, Yonglei Cui, Yan Wang, Xiangge Tian, Lu Zheng, HaiJian Cong, Bin Wu, Xiaokui Huo, Chao Wang, BaoJing Zhang, Xiaobo Wang, Zhonghui Yu
BACKGROUND: Baicalein is the major bioactive flavonoid in some herb medicines and dietary plants; however, the detailed metabolism pathway of its major metabolite oroxylin A-7-O-β-D-glucuronide in human was not clear. It was important to illustrate the major metabolic enzymes that participate in its elimination for the clinic use of baicalein. OBJECTIVES: We first revealed a two-step metabolism profile for baicalein and illustrated the combination of catechol-O-methyltransferase (COMT) and uridine diphosphate-glucuronosyltransferases (UGTs) in drug metabolism, further evaluated its bioactivity variation during drug metabolism...
December 2017: European Journal of Drug Metabolism and Pharmacokinetics
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